Journal of Neural Transmission

, Volume 113, Issue 10, pp 1441–1448 | Cite as

Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson’s disease

  • T. Müller
  • C. Erdmann
  • S. Muhlack
  • D. Bremen
  • H. Przuntek
  • O. Goetze
  • D. Woitalla
Article

Summary.

Addition of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) prolongs plasma metabolism of levodopa (LD). Objectives were to determine the clinical response after EN addition and the plasma degradation of LD and 3-O-methyldopa [3-OMD]. Not optimum treated hospitalised patients with Parkinson’s disease received the same LD dosage on the first day only with carbidopa (CD) and on the second day with CD and EN (t.i.d.) within a standardised setting. We scored motor symptoms and measured LD- and 3-OMD levels on both days at fixed moments. Motor impairment significant better improved probably due to significant higher maximum concentrations [Cmax] and computed area under the curve values of LD levels during the LD/CD/EN condition. Time to Cmax of LD was significantly delayed after the first two LD/CD/EN intakes. An impact of EN on 3-OMD levels appeared. A possibly augmented LD absorption and a prolonged LD metabolism after EN supplementation may contribute to a more continuous LD delivery to the brain.

Keywords: Levodopa, 3-O-methyldopa, entacapone. 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Benetello, P, Furlanut, M, Fortunato, M, Pea, F, Baraldo, M 1997Levodopa and 3-O-methyldopa in cerebrospinal fluid after levodopa-carbidopa associationPharmacol Res35313315PubMedCrossRefGoogle Scholar
  2. Evans, MA, Broe, GA, Triggs, EJ, Cheung, M, Creasey, H, Paull, PD 1981Gastric emptying rate and the systemic availability of levodopa in the elderly parkinsonian patientNeurology3112881294PubMedGoogle Scholar
  3. Fahn, S, Oakes, D, Shoulson, I, Kieburtz, K, Rudolph, A, Lang, A, Olanow, CW, Tanner, C, Marek, K 2004Levodopa and the progression of Parkinson’s diseaseN Engl J Med35124982508PubMedCrossRefGoogle Scholar
  4. Goetz, CG, LeWitt, PA, Weidenman, M 2003Standardized training tools for the UPDRS activities of daily living scale: newly available teaching programMov Disord1814551458PubMedCrossRefGoogle Scholar
  5. Hughes, AJ, Daniel, SE, Kilford, L, Lees, AJ 1992Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 casesJ Neurol Neurosurg Psychiatry55181184PubMedCrossRefGoogle Scholar
  6. Kaakkola, S, Teravainen, H, Ahtila, S, Rita, H, Gordin, A 1994Effect of entacapone, a COMT inhibitor, on clinical disability and levodopa metabolism in parkinsonian patientsNeurology447780PubMedGoogle Scholar
  7. Koller, W, Guarnieri, M, Hubble, J, Rabinowicz, AL, Silver, D 2004An open-label evaluation of the tolerability and safety of Stalevo (R) (carbidopa, levodopa and entacapone) in Parkinson’s disease patients experiencing wearing-offJ Neural Transm112221230PubMedCrossRefGoogle Scholar
  8. Kurlan, R, Rothfield, KP, Woodward, WR, Nutt, JG, Miller, C, Lichter, D, Shoulson, I 1988Erratic gastric emptying of levodopa may cause “random” fluctuations of parkinsonian mobilityNeurology38419421PubMedGoogle Scholar
  9. Männisto, PT, Kaakkola, S, Nissinen, E, Linden, IB, Pohto, P 1988Properties of novel effective and highly selective inhibitors of catechol-O-methyltransferaseLife Sci4314651471PubMedCrossRefGoogle Scholar
  10. Muhlack, S, Woitalla, D, Welnic, J, Twiehaus, S, Przuntek, H, Müller, T 2004Chronic levodopa intake increases levodopa plasma bioavailability in patients with Parkinson’s diseaseNeurosci Lett363284287PubMedCrossRefGoogle Scholar
  11. Müller, T, Voss, B, Hellwig, K, Josef, SF, Schulte, T, Przuntek, H 2004Treatment benefit and daily drug costs associated with treating Parkinson’s disease in a Parkinson’s disease clinicCNS Drugs18105111PubMedCrossRefGoogle Scholar
  12. Müller, T, Woitalla, D, Schulz, D, Peters, S, Kuhn, W, Przuntek, H 2000Tolcapone increases maximum concentration of levodopaJ Neural Transm107113119PubMedCrossRefGoogle Scholar
  13. Murata, M, Kanazawa, I 1997Effects of chronic levodopa therapy on dopa pharmacokineticsEur Neurol385055PubMedGoogle Scholar
  14. Nissinen, E, Tuominen, R, Perhoniemi, V, Kaakkola, S 1988Catechol-O-methyltransferase activity in human and rat small intestineLife Sci4226092614PubMedCrossRefGoogle Scholar
  15. Nutt, JG 1998Catechol-O-methyltransferase inhibitors for treatment of Parkinson’s diseaseLancet35112211222PubMedCrossRefGoogle Scholar
  16. Nutt, JG 2000Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patientsNeurology55S33S37PubMedGoogle Scholar
  17. Olanow, CW, Kieburtz, K, Stern, M, Watts, R, Langston, JW, Guarnieri, M, Hubble, J 2004Double-blind, placebo-controlled study of entacapone in levodopa-treated patients with stable Parkinson diseaseArch Neurol6115631568PubMedCrossRefGoogle Scholar
  18. Papavasiliou, PS, Cotzias, GC, Duby, SE, Steck, AJ, Fehling, C, Bell, MA 1972Levodopa in Parkinsonism: potentiation of central effects with a peripheral inhibitorN Engl J Med286814PubMedGoogle Scholar
  19. Poewe, W 2004The role of COMT inhibition in the treatment of Parkinson’s diseaseNeurology62S31S38PubMedCrossRefGoogle Scholar
  20. Schultz, E, Tarpila, S, Backstrom, AC, Gordin, A, Nissinen, E, Pohto, P 1991Inhibition of human erythrocyte and gastroduodenal catechol-O-methyltransferase activity by nitecaponeEur J Clin Pharmacol40577580PubMedGoogle Scholar
  21. Smith, LA, Jackson, MJ, Hansard, MJ, Maratos, E, Jenner, P 2003Effect of pulsatile administration of levodopa on dyskinesia induction in drug-naive MPTP-treated common marmosets: effect of dose, frequency of administration, and brain exposureMov Disord18487495PubMedCrossRefGoogle Scholar
  22. Waller, DG, Roseveare, C, Renwick, AG, Macklin, B, George, CF 1991Gastric emptying in healthy volunteers after multiple doses of levodopaBr J Clin Pharmacol32691695PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • T. Müller
    • 1
  • C. Erdmann
    • 1
  • S. Muhlack
    • 1
  • D. Bremen
    • 3
  • H. Przuntek
    • 1
  • O. Goetze
    • 2
  • D. Woitalla
    • 1
  1. 1.Department of Neurology, St. Josef HospitalRuhr University BochumBochumGermany
  2. 2.Department of Gastroenterology and HepatologyUniversitätsspital ZürichSwitzerland
  3. 3.Orion Pharma GmbHHamburgGermany

Personalised recommendations